A series of new sugar-modified 2',3'-dideoxy-2',3'-difluoro nucleosides were synthesized and the NMR solution conformations were determined. Specific forms of ring puckering were correlated with anti-HIV activity. A number of novel ring-expanded carbocyclic analogues of the fermentation product oxetanocin A were synthesized and evaluated for anti-HIV activity. As opposed to the dideoxyribose counterparts, these compounds were devoid of anti-HIV activity. Selected acid-stable 6-X-substituted-(2'-fluoro-2', 3'-dideoxy-beta-D-threo-pentofuranosyl)purines (X = F, Cl, Br, I, NHMe, NHEt, NHOH, NHOMe, NHOCH2 Ph) were prepared as anti-HIV adenosine deaminase-activated "pro-drugs". Their evaluation is in progress.